The goal of this proposal is to determine if malignant brain tumors are sensitive to the Chinese herbal remedy Zen Sheng Ping (ZSP, also known as antitumor B). ZSP is a combination of six herbs which has been shown to prevent the progression of pre-neoplastic lesions of the esophagus. It also appears to slow or prevent progression of lung cancer in both humans and in animal models. It was recently found that ZSP downregulates the Notch signaling pathway in lung cancer. The Notch pathway plays a critical role in the proliferation of lung tumor cells, suggesting Notch inhibition is an important mechanism by which the anti-tumor effects of ZSP are mediated. This raises the possibility that ZSP might also successfully treat other Notch- dependant tumors. We have shown that Notch signaling plays a critical role in the growth of several types of brain cancer, including the most common malignant brain tumors in children (medulloblastoma) and adults (glioblastoma). Other Notch-dependent neoplasms that might be treated using ZSP include pancreatic, breast and ovarian carcinomas, as well as melanoma. Small-molecule Notch inhibitors appear block the formation and growth of brain tumor xenografts by depleting stem-like cancer cells, but this class of compounds has been associated with significant toxicity. We therefore plan to investigate whether ZSP might represent a more potent and/or less toxic treatment for malignant brain tumors by blocking Notch activity. Project Narrative: The goal of this proposal is to determine if malignant brain tumors can is treated using a Chinese herbal remedy known as Zen Sheng Ping (ZSP). It was recently found that ZSP inhibits an important molecular pathway known as Notch in cancer cells. We have shown that Notch signaling plays a critical role in the growth of several types of brain cancer, including the most common malignant brain tumors in children (medulloblastoma) and adults (glioblastoma) [unreadable] [unreadable] [unreadable]